小柴胡汤对大鼠肝脏胞液糖皮质激素受体的调节作用

应用放射配体结合法检测了４０只ＳＤ雄性大鼠肝胞液的糖皮质激素受体（ＧＣＲ）。发现单纯使用糖皮质激素（ＧＣ）组和单纯使用小柴胡汤组大鼠ＧＣＲ数目均明显低于对照组（Ｐ＜０．０１），而小柴胡汤与ＧＣ合用组ＧＣＲ数目明显高于单纯使用ＧＣ组（Ｐ＜０．０１）。各组Ｋｄ值无显著差异。提示小柴胡汤既具有ＧＣ样作用，又能使ＧＣ引起的ＧＣＲ降调作用明显减弱。     

体外反搏治疗失血性休克中一氧化氮合酶的变化

目的：探讨反搏治疗失血休克中一氧化氮合酶（ＮＯＳ）的变化。方法：复制狗的失血休克模型，用同位素方法测定反搏前后各组织的ＮＯＳ活性。结果：体外反搏后平均动脉压较反搏前明显上升（Ｐ＜００１）。脑ＮＯＳ测定值假手术对照组明显高于失血休克组Ｐ＜００１）及失血休克克反搏组（Ｐ＜００１），失血休克组则明显低于失血休克反搏组（Ｐ＜００１）；心肌ＮＯＳ活性假手术对照组与失血休克反搏组均明显高于失血休克组（Ｐ＜００５，Ｐ＜００１），但假手术对照组与失血休克反搏组之间无显著差异（Ｐ＞００５）；主动脉ＮＯＳ活性假手术对照组明显高于失血休克组（Ｐ＜００１）及失血休克反搏组（Ｐ＜００５），但失血休克组与失血休克反搏组间无明显差异（Ｐ＞００５）。结论：体外反搏可以增强小血管ＮＯＳ活性，ＮＯＳ活性的恢复则可能在反搏治疗中起重要作用     

白细胞介素—8对大鼠失血性休克血浆6—keto—PGF1α和TXB2含量的影响

目的和方法：本文观察重组人内皮细胞衍生的白细胞介素－８（ｒｈＥＤＩＬ－８）对大鼠晚期失血性休克血浆６－ｋｅｔｏ－ＰＧＦ１α和ＴＸＢ２含量的影响，并与平均动脉血压（ＭＡＢＰ）的变化作相关性分析。结果：晚期失血性休克血浆６－ｋｅｔｏ－ＰＧＦ１α含量明显降低（１０６７４±１２２６ｖｓ１５６８２±１１４２）ｎｇ／Ｌ，Ｐ＜００１，ＴＸＢ２含量明显升高（３１８３６±２６．５４ｖｓ１７４９１±２１５８）ｎｇ／Ｌ，Ｐ＜００１；给予ｒｈＥＤＩＬ－８（２５０μｇ／ｋｇ）后，血浆６－ｋｅｔｏ－ＰＧＦ１α含量明显升高（３６８４７±１５６８ｖｓ１０３７６±１３１８）ｎｇ／Ｌ，Ｐ＜００１，其血浆水平与ＭＡＢＰ变化呈明显正相关（ｒ＝０．７４６，Ｐ＜００１）；ｒｈＥＤＩＬ－８对血浆ＴＸＢ２含量却无明显影响。结论：ｒｈＥＤＩＬ－８抗晚期失血性休克作用与其促进血管内皮细胞产生和释放ＰＧＩ２有关     

内毒素大鼠休克早期血浆组织因子与组织因子途径抑制物的观察

目的：观察内毒素休克早期大鼠血浆ＴＦ、ＴＦＰＩ的变化。结果：静脉给予内毒素的大鼠ＭＡＰ呈进行性下降，至１２０ｍｉｎ时降至（５８±２５）ｋＰａ，ＴＦ含量高于对照组（Ｐ＜００５），而ＴＦＰＩ无显著改变（Ｐ＞００５）。血浆ＴＮＦ含量明显增高（Ｐ＜００１），ＡＴⅢ活性显著低于对照组（Ｐ＜００１）；ＷＢＣ计数减少（Ｐ＜００１），ＰＬ计数无明显改变（Ｐ＞００５）。结论：内毒素休克早期休克组织因子凝血途径易化因素增强，而拮抗因素不变或减弱     

原发性癫痫患者糖皮质激素和糖皮质激素受体改变的研究

用放射配体结合分析，测定了４１例（男１６例，女２５例）原发性癫痫患者外周血白细胞糖皮质激素受体（ｇｌｕｃｏｃｏｒｔｉｃｏｉｄ ｒｅｃｅｐｔｏｒ ＧＲ），同时用放射免疫分析测定了患者血浆皮质醇（Ｆ），即糖皮质激素（ｇｌｕｃｏｃｒｔｉｃｏｉｄＧＣ），并与正常对照组比较。结果表明，无论年龄、性别及服用何种抗痫药物，原发性癫痫患者的ＧＣ都明显高于对照组（Ｐ〈０．０１）；ＧＲ都明显低于对照组，（Ｐ〈０．０     

健胎液对胎儿宫内发育迟缓孕鼠血浆、胎盘NO含量的影响

为从孕鼠血浆和胎盘一氧化氮（ＮＯ）水平探讨中药“健胎液”治疗胎儿宫内发育迟缓（ＩＵＧＲ）的机理，采用被动吸烟法建立ＩＵＧＲ动物模型，应用镀铜镉还原和内标比色法（Ｇｒｅｉｓ法），测定ＩＵＧＲ组、ＩＵＧＲ加健胎液组（用药组）孕鼠血浆及胎盘组织中ＮＯ的稳定代射终产物亚硝酸基／硝酸基（ＮＯ－２／ＮＯ－３）含量，并以正常孕鼠作对照。结果：与正常对照组和用药组相比，ＩＵＧＲ组胎鼠平均出生体重显著降低（Ｐ＜００１），ＩＵＧＲ组血浆及胎盘组织中ＮＯ－２／ＮＯ－３含量均显著降低（Ｐ＜００５～００１），而用药组和正常组相比，胎鼠平均出生体重、血浆及胎盘组织中ＮＯ－２／ＮＯ－３含量均无显著性差异（Ｐ＞００５）。结论：胎儿宫内发育迟缓的发生与ＮＯ的合成和释放显著降低，因而影响胎盘微循环，限制了母儿宫内发育迟缓。     

补肾定喘汤对哮喘大鼠糖皮质激素受体的影响

采用放射性配基竞争结合法，测定连续激光哮喘大鼠服用补肾定喘哮汤后第１、３、７天肺组织糖皮质激素受体（ＧＣＲ）。观察结果发现：激发后第１天中药组大鼠肺组织ＧＣＲ较正常对照组显著升高（Ｐ〈０．０１）；第３天中药组大鼠肺组织ＧＣＲ仍维持较高水平，与模型组比差异显著（Ｐ〈０．０１）；第７天中药组及中药加西药组大鼠肺组织ＧＣＲ水平较模型组均有显著差异（Ｐ〈０．０１），提示中药补肾定喘汤大鼠肺组织ＧＣＲ水平具     

失血性休克再灌注后血浆内皮素的变化及磷脂酶A_2阻断剂对它的影响

家兔出血性休克再灌注（Ｓ／Ｒ）后，放免分析发现血浆内皮素逐渐升高，同失血前比较第６ｈ有显著差异（Ｐ＜０．０５），假手术组没有改变。磷脂酶Ａ_２阻断剂氯喹、磷酸萘酚喹和抗氧化剂黄芪酮于失血后再灌注前使用可抑制Ｓ／Ｒ后２ｈ内血浆内皮素增高，后两者可更明显降低Ｓ／Ｒ后３０ｍｉｎ的内皮索水平，与失血前比较差异非常好著（Ｐ＜０．０１）。同时，ＨＣＯ~－_３和碱贮备（ＳＢＣ）显著降低，上述三种药物治疗显著增加ＨＣＯ~－_３和ＳＢＣ的含量，它们在Ｓ／Ｒ后２４ｈ明显高于Ｓ／Ｒ组的水平（Ｐ＜０．０１）。结果提示，Ｓ／Ｒ后血浆内皮素上升可能与代谢性酸中毒加重有一定联系。磷脂酶Ａ_２阻断剂和抗氧化剂可能通过早期抑制内皮素的释放，从而减轻２４ｈ后代谢性酸中毒程度。     

尿毒症患者多形核白细胞糖皮质激素受体与趋化移动的改变及意义

应用放射配体结合分析，检测尿毒症患者外周血多形核白细胞（ＰＭＬ）的糖皮质激素受体（ＧＲ），尿毒症患者ＰＭＬＧＲ的最大结合容量（Ｂｍａｘ）明显低于对照组，而其解离常数（Ｋｄ）比对照组的显著升高。同时检测ＧＲ的效应指标：皮质醇（Ｆ）对ＰＭＬ的趋化移动（ＣｈｔＭ）的抑制率（ＦＩ），Ｆ对ＣｈｔＭ的ＦＩ明显低于对照组，与降低的ＧＲ呈正相关（ｒ＝０．７８５，Ｐ＜０．０１）．尿毒症患者ＰＭＬ的ＧＲ降低的同时，伴效应指标的改变，表明ＧＲ的降低具有临床意义。尿毒症患者ＰＭＬ的随机移动（ＲＭ）和ＣｈｔＭ均明显降低，提示白细胞功能降低。     

胶质瘤细胞血小板源生长因子B链的纯合二聚体与其受体基因表达和受体活化水平的研究

目的探讨胶质瘤细胞血小板源生长因子Ｂ链的纯合二聚体（ＰＤＧＦＢＢ）及其受体（ＰＤＧＦＲ）基因表达和ＰＤＧＦＲ活化水平在胶质瘤发生、发展中的作用。方法用原位杂交和免疫组化染色观察了７３例不同级别的人胶质瘤组织标本。结果６２例（８４９％）的肿瘤细胞表达ＰＤＧＦＢｍＲＮＡ，其阳性率和阳性肿瘤细胞含量均随肿瘤恶性程度升高而递增。ＰＤＧＦＲα、ＰＤＧＦＲβ和这两种受体及其信号传递通路活化标记物酪氨酸磷酸化蛋白（ＰＴｙｒ）的阳性率均为１００％。这３种阳性肿瘤细胞密度（个／００５ｍｍ２）彼此间均呈正相关（ｒ＝０８３８～０８９７，Ｐ＜００１），并均随肿瘤恶性程度及肿瘤细胞ＰＤＧＦＢｍＲＮＡ表达水平升高而同步增加，差异均有显著性（Ｐ＜００５～００１）。但各肿瘤组内两种受体阳性肿瘤细胞密度间无显著性差异（Ｐ＞００５）。结论胶质瘤细胞普遍存在ＰＤＧＦＢＢ自分泌环，ＰＤＧＦＲα和ＰＤＧＦＲβ在该自分泌环中均起重要作用，该自分泌环活性异常增加可能对ＰＤＧＦＢＢ及其受体表达有正反馈诱导作用，并可能在胶质瘤发生及恶性进展过程中发挥重要作用。     

硫化氢在休克肠淋巴液致肝损伤中的作用与机制

 目的： 应用硫化氢（H2S）合成酶胱硫醚γ-裂解酶（CSE）抑制剂DL-炔丙基甘氨酸（PPG）和H2S供体硫氢化钠（NaHS）作用于行肠淋巴液引流的大鼠,探讨H2S在肠淋巴液引流减轻休克大鼠肝损伤中的作用。方法：休克组、休克+引流组、休克+引流+PPG组（45 mg/kg,放血前0.5 h,ip）和休克+引流+NaHS（28 μmol/kg,放血前0.5 h,ip）组大鼠复制失血性休克模型,低血压1 h后行液体复苏,休克+引流组、休克+引流+PPG组和休克+引流+NaHS组在输液结束后,行肠淋巴液引流至液体复苏结束后3 h。观察肝组织形态,检测血浆肝功能生化指标以及肝组织H2S、CSE、Toll样受体4（TLR4）、白细胞介素（IL）-10、IL-12和肿瘤坏死因子α（TNF-α）水平。结果：休克组大鼠血浆天门冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、总胆汁酸（TBA）以及肝组织H2S、CSE、TLR4、IL-10、IL-12、TNF-α含量均显著高于假手术组;肠淋巴液引流显著降低了休克组大鼠血浆AST、ALT、TBA以及肝组织H2S、CSE、IL-10、IL-12、TNF-α含量;PPG使休克+引流组大鼠血浆AST、ALT、TBA以及肝组织H2S、TLR4、IL-10、IL-12、TNF-α含量进一步降低;NaHS则提高了休克+引流组大鼠血浆AST、ALT与肝组织H2S、TLR4、IL-10、IL-12、TNF-α的含量。组织形态学观察表明,休克组和休克+引流+NaHS组大鼠出现了肝细胞损伤,假手术组、休克+引流组、休克+引流+PPG组大鼠肝细胞形态基本正常。结论：肠淋巴液引流减轻失血性休克大鼠肝损伤的作用机制与抑制H2S生成、减轻H2S介导的炎症反应有关。     

2型糖尿病大鼠脑内11β-HSD1和GR的表达与认知功能的关系及棉酚的干预作用

目的：研究棉酚对2型糖尿病大鼠认知功能的影响,并探讨其作用机制。方法：雄性SD大鼠30只,随机均分成3组：正常组、2型糖尿病组、棉酚治疗组。后2组给予高脂饮食加小剂量(30 mg/kg)链脲佐菌素(STZ)诱导2型糖尿病模型,棉酚治疗组(第1-4周按15 mg·kg-1·d-1剂量棉酚灌胃,第5-12周按每周15 mg·kg-1剂量棉酚灌胃)。用 Morris 水迷宫测试大鼠行为学;生化检测血糖及ELISA法检测血皮质酮、放免法检测血胰岛素水平;Western blotting方法检测大脑皮层及海马组织11β-羟基类固醇脱氢酶1（11β-HSD1）、糖皮质激素受体（GR）蛋白表达水平;电镜、光镜下观察大脑皮层及海马组织的形态学改变。 结果：与正常组比较,糖尿病组大脑皮层及海马神经元可见较明显的核固缩、高尔基体扩张、线粒体水肿,血糖、血皮质酮、血胰岛素水平显著升高(P<0.01),GR蛋白表达明显降低（P<0.05）,11β-HSD1蛋白表达呈升高趋势,行为测试潜伏期显著延长（P<0.01）,搜索策略明显变差（P<0.01）;经棉酚干预后,大脑皮层及海马组织病理改变较轻,血糖、血皮质酮、血胰岛素水平显著降低(P<0.01),GR蛋白表达明显升高（P<0.05）,11β-HSD1蛋白表达明显降低（P<0.05）,行为测试潜伏期显著缩短（P<0.01）,搜索策略显著好转（P<0.01）。 结论：棉酚能改善2 型糖尿病大鼠的认知功能,可能与降低2型糖尿病大鼠脑内11β-HSD1 蛋白、升高GR蛋白水平有关。     

Receptor mechanisms for realizing the effect of glucocorticoid hormones in traumatic and hemorrhagic shock

Blood corticosterone concentrations showed a 2-fold increase in traumatic and hemorrhagic shock. Following 4 hours of injury, the rat hepatic cytasol density of glucocorticoidal receptor II and III decreased to 76 and 67% of the level of intact animals, respectively. There were changes in the physicochemical properties of glucocorticoidal receptors: an increase in Ka and a decrease in Kd of the hormone-receptor complexes. A direct relation was found of the glucocorticoid-binding capacity of receptors II to blood pressure (BP) in shock. The most marked suppression of receptors II was noted in hemorrhagic shock, which seems to be due to more profound systemic hemodynamic changes and low BP in this type of shock. There was a concurrent reduction in the density of receptors I and II up to the certain decrease in the levels of receptors II, then was an increase in receptor III binding of [3H]-corticosterone. With the low density of receptors II and with the high concentration of corticosterone, this appears to be aimed at preserving the glucocorticoid-dependent activation of the cell genetic apparatus. Dysfunctions found in the glucocorticoidal receptors are a cause of the development of relative glucocorticoid deficiency in shock.     

几种血管活性药物对失血性休克大鼠肠系膜微循环的影响

目的:比较几种血管活性药物对失血性休克大鼠肠系膜微循环的影响。方法:选取SD大鼠,随机分为正常对照组(A组),失血性休克模型组(B组),生理盐水处理组(C组),多巴胺处理组(D组),去甲肾上腺素处理组(E组),山莨菪碱处理组(F组)。实验采用动脉放血至动脉血压为60mmHg左右,同时观察肠系膜微循环状态改变来复制失血性休克大鼠模型;各组行相应药物处理后,分别测量动脉血压和检测肠系膜微循环相关指标,并进行比较分析。结果:B组大鼠动脉血压、肠系膜微血管出/入口管径、血流速度明显低于A组(P<0.05或P<0.01),血液流态由线流改变为粒流。与B组比较,几种血管活性药物(D、E、F组)对失血性休克大鼠动脉血压均有显著升高作用,依次为去甲肾上腺素>多巴胺>山莨菪碱(P<0.05或P<0.01),多巴胺对微血管出/入口管径恢复明显(P<0.01),山莨菪碱和多巴胺对肠系膜血流速度有明显改善(P<0.01或P<0.05),山莨菪碱还能使肠系膜血流流态恢复为线流。结论:实验性治疗失血性休克需适度补充血容量,同时选用山莨菪碱改善肠系膜微循环,有利于休克复苏。     

人促红细胞生成素对肾缺血再灌注损伤的保护作用

目的 探讨促红细胞生成素(erythropoietin, Epo)对失血性休克大鼠肾损伤的保护作用.方法 建立失血性休克大鼠肾损伤模型,分为对照组、休克组及Epo治疗组3组,进行组织学观察,并检测血丙二醛(MDA)、肌酐(Cr)、素氮(BUN)和肾组织匀浆超氧化物歧化酶(SOD)、白介素-6(IL-6)水平.结果 Epo治疗组血浆MDA、Cr、BUN水平较失血性休克组组显著下降(P＜0.05);肾组织匀浆SOD显著升高、IL-6显著降低(P＜0.05).结论 Epo可提高SOD,降低IL-6,对肾缺血再灌注损伤具有保护作用.     

从氧自由基、一氧化氮探讨四逆汤抗急性失血性休克的肝脏机制

目的:从氧自由基、一氧化氮探讨四逆汤抗急性失血性休克的肝脏机制。方法:复制急性失血性休克大鼠模型, 分为假手术对照组;单纯休克模型组;休克+生理盐水复苏组;休克+四逆注射液复苏组。四逆注射液(浓度1000g生药/L), 剂量0.1mL/200g大鼠。用生理盐水或四逆注射液治疗3h后处死动物并取组织。测定各组肝脏超氧化物歧化酶(SOD)活性、丙二醛(MDA)水平, 一氧化氮(NO)水平。采用免疫组化染色法, 观察诱导型一氧化氮合酶(iNOS)在肝细胞中的变化特点。RT-PCR观测肝细胞iNOS和内皮源性一氧化氮合酶(eNOS)基因表达的变化。结果:模型组在休克1h后SOD活性明显低于对照组(P＜0.01)、MDA水平明显高于对照组(P＜0.01)。四逆汤组复苏3h后肝组织SOD明显高于生理盐水组(P＜0.01)、MDA低于生理盐水组(P＜0.01)、NO水平明显高于生理盐水组(P＜0.01)。生理盐水组iNOS在肝细胞中染色阳性单位明显高于四逆汤组(P＜0.05)。生理盐水组促进iNOSmRNA的表达。四逆汤组eNOSmRNA的表达增强。结论:四逆汤通过清除氧自由基, 升高NO, 改善肝组织微循环, 减少诱导型iNOS表达的各种因素, 理论上减轻了NO与氧自由基生成的ONOO的细胞毒作用和血管的低反应性, 并对肝脏起到保护作用。     

Plasma catecholamines, cyclic AMP and metabolic substrates in hemorrhagic shock of the rat. The effect of adrenal demedullation and 6-OH-dopamine treatment.

Plasma catecholamines, cyclic AMP and metabolic substrates in hemorrhagic shock of rats was studied in 4 groups of animals: 1) Control rats, 2) rats with adrenal demedullation, 3) rats with 6-OH-dopamine induced chemical sympathectomy, and 4) rats with combined demedullation and sympathectomy. The rats were bled to a systemic blood pressure of 35 mmHg. The basal plasma level of noradrenaline (NA), adrenaline (A) and dopamine (DA) in control animals was each about 1 nmol/1. After hemorrhage for 1 h the A levels had reached 50 nmol/l and there was little further rise after 4 h. The rise was eliminated by demedullation but unaffected by sympathectomy. NA levels rose continuously in the control and in the sympathectomized rats. At 1 h the level was about 4 nmol/l and at 4 h about 20 nmol/l. The demedullated rats showed a 3-fold increase in circulating NA, while little or no change was seen in the combined demedullated and sympathectomized rats. DA levels did not change in any of the groups during the first hour, but were markedly elevated after 4 h of hypotension. Cyclic AMP and glucose levels in plasma showed a rapid increase 1 h after hemorrhage and thereafter returned to or below basal values. Demedullation largely prevented the increase, while sympathectomy had no effect. The increase in lactate and pyruvate levels were diminished but not eliminated by either sympathectomy or demedullation. Glycerol levels were unchanged and FFA decreased in all groups of rats. The results show that the adrenal medulla is the dominating source of plasma catecholamines in hemorrhagic shock in rats. The initial increase in plasma glucose and cyclic AMP appear to be largely mediated by adrenal A. The subsequent fall in these parameters and derangement of circulatory homeostasis are not, in the present shock model, primarily due to a failure of catecholamine secretion, but rather to a decreased responsiveness of peripheral tissues to catecholamine stimulation.     

Plasma catecholamines,cyclic AMP and metabolic substrates in hemorrhagic shock of the rat. The effect of adrenal demedullation and 6-OH-dopamine treatment

Plasma catecholamines, cyclic AMP and metabolic substrates in hemorrhagic shock of rats was studied in 4 groups of animals: 1) Control rats, 2) rats with adrenal demedullation, 3) rats with 6-OH-dopamine induced chemical sympathectomy, and 4) rats with combined demedullation and sympathectomy. The rats were bled to a systemic blood pressure of 35 mmHg. The basal plasma level of noradrenaline (NA), adrenaline (A) and dopamine (DA) in control animals was each about 1 nmol/1. After hemorrhage for 1 h the A levels had reached 50 nmol/1 and there was little further rise after 4 h. The rise was eliminated by demedullation but unaffected by sympathectomy. NA levels rose continuously in the control and in the sympathectomized rats. At 1 h the level was about 4 nmol/1 and at 4 h about 20 nmol/1. The demedullated rats showed a 3-fold increase in circulating NA, while little or no change was seen in the combined demedullated and sympathectomized rats. DA levels did not change in any of the groups during the first hour, but were markedly elevated after 4 h of hypotension. Cyclic AMP and glucose levels in plasma showed a rapid increase 1 h after hemorrhage and thereafter returned to or below basal values. Demedullation largely prevented the increase, while sympathectomy had no effect. The increase in lactate and pyruvate levels were diminished but not eliminated by either sympathectomy or demedullation. Glycerol levels were unchanged and FFA decreased in all groups of rats. The results show that the adrenal medulla is the dominating source of plasma catecholamines in hemorrhagic shock in rats. The initial increase in plasma glucose and cyclic AMP appear to be largely mediated by adrenal A. The subsequent fall in these parameters and derangement of circulatory homeostasis are not, in the present shock model, primarily due to a failure of catecholamine secretion, but rather to a decreased responsiveness of peripheral tissues to catecholamine stimulation.     

Phenytoin and electric shock-induced apoptosis in rat peripheral blood lymphocytes

The apoptotic index (AI) of peripheral blood lymphocytes (PBL) and plasma corticosterone (CS) levels were determined in Wistar rats treated with phenytoin (PHT) at therapeutic and toxic doses (100 or 200 mg/kg/day, respectively, over a period of 7 days) and stressed by bifrontal electric shock (60 Hz/40 mA/0.2 seg). The values of CS and AI were found to be significantly higher in rats submitted to electric shock (ES) and in rats treated with therapeutic and toxic doses of PHT plus ES, than in rats treated only with PHT (P<0.001). The plasma concentrations of PHT were found to be significantly higher in rats treated with toxic doses than in those treated with therapeutic doses (P<0.001), while the control group (without treatment) and vehicle group (propilenglycol-ethanol-water, 40:10:50), showed low levels of CS, and less than 1% of AI. The DNA analysis by electrophoresis in agarose in all the groups was positive, displaying the ladder pattern characteristic of apoptotic process (200 bp), except in the control groups (no treatment and vehicle treated). Our results demonstrate that chronic stress, caused by ES, produces an elevation of CS. The values of apoptosis were correlated with the CS levels, suggesting that the apoptotic inductor process is a consequence of an increase in the concentration of corticosterone in plasma, in response to the hypothalamic-pituitary-adrenals (HPA) axis activation, while phenytoin at therapeutic doses is only a moderate apoptosis inductor.     

Effects of controllable vs. uncontrollable chronic stress on stress-responsive plasma hormones.

We have previously reported effects of chronic stress on circadian rhythms of temperature, eating, and locomotor activity. These studies were conducted using an around-the-clock signalled intermittent footshock paradigm in which some rats have control over shock termination while other rats are yoked to the rats with control. Although this paradigm is stressful, as suggested by decreases in food intake and disrupted circadian rhythms, rats tolerate the paradigm well, continuing to eat, drink, gain weight, and groom. In the present studies, rats were sacrificed following 3 or 14 days of stress, and plasma was collected for hormonal assays. After 3 days of stress, plasma corticosterone and prolactin levels were elevated in both stress groups compared to controls; yoked rats had higher levels of corticosterone than rats in the group with control over shock termination, while prolactin levels in both stressed groups were similar. ACTH levels were similar in stressed and control rats. After 14 days of stress, ACTH and corticosterone levels in both stress groups were similar to control levels. Prolactin levels were elevated in the yoked experimental group compared to levels in control or controllable stress groups. These data support previous studies suggesting that control over stressors attenuates the effects of stress on physiology and demonstrate that two hormones with diverse biological effects are elevated by chronic stress.